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Altered expression of apoptosis-related, circulating cell-free miRNAs in children with familial Mediterranean fever: a cross-sectional study

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Abstract

Objectives

Familial Mediterranean Fever (FMF) is the most common hereditary autoinflammatory disorder characterized by recurrent fever and serositis episodes. Identification of low penetrant or heterozygous MEFV mutations in clinically diagnosed FMF patients did raise a concern on whether epigenetic or environmental factors play an additional role in FMF pathogenesis. We aimed to investigate the expression profile of apoptosis-related miRNAs in FMF and their influence on clinical manifestations in the present study.

Method

191 pediatric FMF patients and 31 healthy children included in the study. Expressions of 33 apoptosis-related, circulating cell-free miRNAs were evaluated by a quantitative polymerase chain reaction, statistically calculated within ΔΔCt values and fold changes were evaluated by Welch T test, in which p < 0.05 were considered to be significant.

Results

Nineteen miRNAs, including let-7a-5p, let-7c, let-7 g-5p, miR-15b-5p, miR-16-5p, miR-17-5p, miR-23a-3p, miR-24-3p, miR-25-3p, miR-26a-5p, miR-26b-5p, miR-27a-3p, miR-29c-3p, miR-30a-5p, miR-30d-5p, miR-30e-5p, miR-106b-5p, miR-146a-5p, and miR-195-5p, were found down-regulated; miR-15a-5p, miR-29b-3p, miR-181a-5p, miR-181b-5p, miR-181c-5p, miR-214-3p, and miR-365a-3p were up-regulated in FMF patients. In detail, these miRNAs were similar among FMF patients in terms of genotype, colchicine response, and having an inflammatory attack during analysis.

Conclusion

We found that 26 apoptosis-related circulating miRNAs were deregulated in children with FMF. Thus, we speculate that these miRNAs have a role in FMF pathogenesis via apoptotic mechanisms.

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Acknowledgements

We specially thank to Aidan Boga (Brisbane, Australia) for his excellent work on language editing of the paper.

Funding

This work was supported by the grants from the Cukurova University Scientific Research Projects Coordination Unit (TTU-2017-7994), Adana, Turkey.

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Authors and Affiliations

  1. Department of Pediatrics, Faculty of Medicine, Cukurova University, Adana, Turkey

    Emin Murat Karpuzoglu

  2. Department of Pediatric Rheumatology, Faculty of Medicine, Cukurova University, Adana, Turkey

    Rabia Miray Kisla Ekinci, Sibel Balci & Mustafa Yilmaz

  3. Department of Medical Genetics, Faculty of Medicine, Cukurova University, Adana, Turkey

    Atil Bisgin

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  1. Emin Murat Karpuzoglu
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  2. Rabia Miray Kisla Ekinci
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Contributions

Dr. Karpuzoglu and Dr. Yilmaz conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript. Dr. Kisla Ekinci, Dr. Bisgin, and Dr. Balci collected data carried out the initial analyses, and critically reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work. All co-authors take full responsibility for the integrity of the study.

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Correspondence to Emin Murat Karpuzoglu.

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Authors declare that they have no conflicts of interest. All co-authors take full responsibility for the integrity of the study.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from parents of the participants included in the study.

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Karpuzoglu, E.M., Kisla Ekinci, R.M., Balci, S. et al. Altered expression of apoptosis-related, circulating cell-free miRNAs in children with familial Mediterranean fever: a cross-sectional study. Rheumatol Int 41, 103–111 (2021). https://doi.org/10.1007/s00296-020-04541-4

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